A computational biologist's personal views on new technologies & publications on genomics & proteomics and their impact on drug discovery

Tuesday, April 05, 2016

Protein Homeostasis: Has it Hit The Classrooms Yet?

I wrote a piece earlier this year suggesting that introductory Biology textbooks should emphasize protein complexes more. My basis for assuming that they generally don't isn't very good: a single textbook in use in TNG's high school class, which sports a copyright date from a decade ago. I also remember what I was taught in high school and college courses, which I would rate as not bad and truly excellent (respectively), plus I was a teaching fellow for one semester of intro bio at Harvard. I now have another suggestion to cram into every biology course: an overview of ubiquitin-proteasome system.

Now, I know the proteasome wasn't mentioned in my high school class, as that was based on a textbook written before the proteasome was discovered. Nor did I ever hear of it as an undergraduate, and don't really remember any contact with it until Millennium acquired Leukocyte, which had only just a bit earlier acquired ProScript, which was attempting to develop a proteasome inhibitor (then called PS-341) as a therapeutic. As has been oft told, Millennium didn't really mean to acquire PS-341; it came along for the ride. PS-341 would go through many near-death experiences until a positive signal emerged in an NCI trial, which sparked interest at Millennium. The drug would go on to be developed as Velcade, which has become an important compound in the treatment of certain hematologic cancers and has sparked competitors and follow-ons. A quick note for the perpetually suspicious: I don't have any ongoing financial interest in proteasome inhibition, nor can I claim any glory from the efforts that got Velcade to patients.

When I reflect back on how intro bio is taught, or at least IMHO should be taught, then perhaps the most fundamental principal is homeostasis: the tendency of biological systems to hold steady. Another key principal are chemical cycles: since matter cannot be created or destroyed, molecules must be built up and torn down.

While at the level of ecology or digestion the breaking down is mentioned, at the level of normal cellular function the topic never was broached in any class I could remember. Lots of time on how translation works -- but if proteins are created, how are they destroyed? So there's a yin-yang aspect that was out-of-balance. The whole concept of proteins having a life cycle was missing. That's another aspect I like: different levels of biology have different cycles of creation and destruction. Organisms eat other organisms, phagocytes eat other cells -- and now proteasomes eat proteins.

Furthermore, once a means for destroying proteins is introduced, then the idea of destroying them on demand to accomplish a task is easy to inject. This, of course, has many real-world counterparts, from fuses that melt to the explosive bolts which allow rocket stages to separate (okay, perhaps mostly geeky real-world examples). While the concept of protein life cycles was never discussed, mitosis was -- and that clearly involves things like asters and spindles forming and then disappearing. When they disappear, where do they go? That would be a great challenge question for students, to get them thinking and wondering -- are they destroyed or do they disperse?

Of course, the challenge is what to boot, for the reality is that the book is already insanely crammed with information, and very little of it is truly expendable (there's a few pages on screening DNA libraries with radioactive probes that could be given the heave-ho, but not much else). And, for better or worse (and probably mostly worse), the content taught is driven by standardized exams and content requirements, which in the best cases are made by committees moving at a snail's pace (which is bad, but sure beats religious zealots in Texas making the calls). So it won't be easy to add the destruction of proteins into curricula, but it sure would give students a more rounded foundation than does the omission of such topics.

1 comment:

Anonymous
said...

I'm pretty sure that ubiquitination is a standard topic in intro bio courses now. Of course, it wasn't when I took high school bio in 1967–8, but it was when I retook biology about 10–15 years ago (otherwise, why would I know anything about it). I don't see any mention of it in the latest AP Biology curriculum, so I agree that it is a apparently not being required.

About Me

Dr. Robison spent 10 years at Millennium Pharmaceuticals working with various genomics & proteomics technologies & working on multiple teams attempting to apply these throughout the drug discovery process. He spent 2 years at Codon Devices working on a variety of protein & metabolic engineering projects as well as monitoring a high-throughput gene synthesis facility. After a brief bit of consulting, he rejoined the cancer drug discovery field at Infinity Pharmaceuticals in May 2009. In September 2011 he joined Warp Drive Bio, a startup applying genomics to natural product drug discovery. Other recurring characters in this blog are his loyal Shih Tzu Amanda and his teenaged son alias TNG (The Next Generation).
Dr. Robison can be reached via his Gmail account, keith.e.robison@gmail.com
You can also follow him on Twitter as @OmicsOmicsBlog.